Despite the prevalence of hypertension and coronary artery disease in patients with diabetes, it now appears that diabetes causes a separate and perhaps distinct cardiomyopathy. This results in a disproportionately high prevalence of congestive failure in diabetic patients and perhaps premature death from coronary artery disease. There has been very little investigation on this specific myocardial component. The proposed project would study the effect of chronic diabetes created with the use of streptozotocin or alloxan in rats. Studies would be performed using the isolated working rat heart to investigate ventricular function, myocardial performance and myocardial metabolism simultaneously under highly controlled conditions, and in response to increasing preload, afterload and paired pacing and to perfusions with different substrates and insulin. Parallel studies would be conducted in vivo in the open-chest rat to determine the effect of diabetic blood on cardiac function. The studies would be conducted in normoglycemic, hyperglycemic and hyperlipidemic hearts from these animals and in diabetic animals treated with insulin. Any abnormalities in myocardial function would eventually be investigated for possible mechanisms. In the initial grant the focus would be on measurement of energy supply, energy storage, and energy demand. Myocardial oxygen delivery would be studied in the isolated perfused rat heart system. Endogenous high energy phosphate stores would be measured. The effects of myocardial ischemia on cardiac function would also be examined. It is expected that these studies will provide useful basic information regarding the response of hearts to diabetes, and point to possible direct ways in which patients with diabetes might be protected from this cardiac complication.